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Vaccine protection against Zika virus from Brazil

机译：预防巴西寨卡病毒的疫苗

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摘要

Zika virus (ZIKV) is a flavivirus that is responsible for the current epidemic in Brazil and the Americas(1,2). ZIKV has been causally associated with fetal microcephaly, intrauterine growth restriction, and other birth defects in both humans(3-8) and mice(9-11). The rapid development of a safe and effective ZIKV vaccine is a global health priority(1,2), but very little is currently known about ZIKV immunology and mechanisms of immune protection. Here we show that a single immunization with a plasmid DNA vaccine or a purified inactivated virus vaccine provides complete protection in susceptible mice against challenge with a strain of ZIKV involved in the outbreak in northeast Brazil. This ZIKV strain has recently been shown to cross the placenta and to induce fetal microcephaly and other congenital malformations in mice(11). We produced DNA vaccines expressing ZIKV pre-membrane and envelope (prM-Env), as well as a series of deletion mutants. The prM-Env DNA vaccine, but not the deletion mutants, afforded complete protection against ZIKV, as measured by absence of detectable viraemia following challenge, and protective efficacy correlated with Env-specific antibody titers. Adoptive transfer of purified IgG from vaccinated mice conferred passive protection, and depletion of CD4 and CD8 T lymphocytes in vaccinated mice did not abrogate this protection. These data demonstrate that protection against ZIKV challenge can be achieved by single-shot subunit and inactivated virus vaccines in mice and that Env-specific antibody titers represent key immunologic correlates of protection. Our findings suggest that the development of a ZIKV vaccine for humans is likely to be achievable.
机译：寨卡病毒（ZIKV）是一种黄病毒，是造成巴西和美洲当前流行的原因（1,2）。 ZIKV与人类（3-8）和小鼠（9-11）的胎儿小头畸形，宫内生长受限以及其他先天缺陷有因果关系。安全有效的ZIKV疫苗的快速发展是全球健康的重中之重（1,2），但目前对ZIKV免疫学和免疫保护机制知之甚少。在这里，我们显示了用质粒DNA疫苗或纯化的灭活病毒疫苗进行的单次免疫可为易感小鼠提供完全保护，使其免受巴西东北部爆发的ZIKV毒株的攻击。最近发现这种ZIKV株可穿过胎盘并诱发小鼠的胎儿小头畸形和其他先天畸形（11）。我们生产了表达ZIKV前膜和包膜（prM-Env）以及一系列缺失突变体的DNA疫苗。 prM-Env DNA疫苗，而不是缺失突变体，提供了针对ZIKV的完全保护，通过攻击后不存在可检测的病毒血症来衡量，并且其保护功效与Env特异性抗体滴度相关。从疫苗接种的小鼠中纯化的IgG的过继转移赋予了被动保护作用，而在疫苗接种的小鼠中CD4和CD8 T淋巴细胞的消耗却没有消除这种保护作用。这些数据表明，针对ZIKV攻击的保护可以通过单次亚基和灭活病毒疫苗在小鼠中实现，并且Env特异性抗体滴度代表了保护的关键免疫学关联。我们的发现表明，针对人类的ZIKV疫苗的开发是可以实现的。

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  • 来源
    《Nature》 |2016年第7617期|474-478|共5页
  • 作者

    Larocca Rafael A.; Abbink Peter; Peron Jean Pierre S.; Zanotto Paolo M. de A.; Iampietro M. Justin; Badamchi-Zadeh Alexander; Boyd Michael; Nganga David; Kirilova Marinela; Nityanandam Ramya; Mercado Noe B.; Li Zhenfeng; Moseley Edward T.; Bricault Christine A.; Borducchi Erica N.; Giglio Patricia B.; Jetton David; Neubauer George; Nkolola Joseph P.; Maxfield Lori F.; De La Barrera Rafael A.; Jarman Richard G.; Eckels Kenneth H.; Michael Nelson L.; Thomas Stephen J.; Barouch Dan H.;

  • 作者单位

    Harvard Med Sch, Beth Israel Deaconess Med Ctr, Ctr Virol & Vaccine Res, Boston, MA 02215 USA;

    Harvard Med Sch, Beth Israel Deaconess Med Ctr, Ctr Virol & Vaccine Res, Boston, MA 02215 USA;

    Univ Sao Paulo, BR-05508000 Sao Paulo, Brazil;

    Univ Sao Paulo, BR-05508000 Sao Paulo, Brazil;

    Harvard Med Sch, Beth Israel Deaconess Med Ctr, Ctr Virol & Vaccine Res, Boston, MA 02215 USA;

    Harvard Med Sch, Beth Israel Deaconess Med Ctr, Ctr Virol & Vaccine Res, Boston, MA 02215 USA;

    Harvard Med Sch, Beth Israel Deaconess Med Ctr, Ctr Virol & Vaccine Res, Boston, MA 02215 USA;

    Harvard Med Sch, Beth Israel Deaconess Med Ctr, Ctr Virol & Vaccine Res, Boston, MA 02215 USA;

    Harvard Med Sch, Beth Israel Deaconess Med Ctr, Ctr Virol & Vaccine Res, Boston, MA 02215 USA;

    Harvard Med Sch, Beth Israel Deaconess Med Ctr, Ctr Virol & Vaccine Res, Boston, MA 02215 USA;

    Harvard Med Sch, Beth Israel Deaconess Med Ctr, Ctr Virol & Vaccine Res, Boston, MA 02215 USA;

    Harvard Med Sch, Beth Israel Deaconess Med Ctr, Ctr Virol & Vaccine Res, Boston, MA 02215 USA;

    Harvard Med Sch, Beth Israel Deaconess Med Ctr, Ctr Virol & Vaccine Res, Boston, MA 02215 USA;

    Harvard Med Sch, Beth Israel Deaconess Med Ctr, Ctr Virol & Vaccine Res, Boston, MA 02215 USA;

    Harvard Med Sch, Beth Israel Deaconess Med Ctr, Ctr Virol & Vaccine Res, Boston, MA 02215 USA;

    Harvard Med Sch, Beth Israel Deaconess Med Ctr, Ctr Virol & Vaccine Res, Boston, MA 02215 USA;

    Harvard Med Sch, Beth Israel Deaconess Med Ctr, Ctr Virol & Vaccine Res, Boston, MA 02215 USA;

    Harvard Med Sch, Beth Israel Deaconess Med Ctr, Ctr Virol & Vaccine Res, Boston, MA 02215 USA;

    Harvard Med Sch, Beth Israel Deaconess Med Ctr, Ctr Virol & Vaccine Res, Boston, MA 02215 USA;

    Harvard Med Sch, Beth Israel Deaconess Med Ctr, Ctr Virol & Vaccine Res, Boston, MA 02215 USA;

    Walter Reed Army Inst Res, Silver Spring, MD 20910 USA;

    Walter Reed Army Inst Res, Silver Spring, MD 20910 USA;

    Walter Reed Army Inst Res, Silver Spring, MD 20910 USA;

    Walter Reed Army Inst Res, Silver Spring, MD 20910 USA;

    Walter Reed Army Inst Res, Silver Spring, MD 20910 USA;

    Harvard Med Sch, Beth Israel Deaconess Med Ctr, Ctr Virol & Vaccine Res, Boston, MA 02215 USA|Ragon Inst MGH MIT & Harvard, Cambridge, MA 02139 USA;

  • 收录信息 美国《科学引文索引》(SCI);美国《工程索引》(EI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
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